Rayman Joseph B, Kandel Eric R
Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Cold Spring Harb Perspect Biol. 2017 Jan 3;9(1):a023671. doi: 10.1101/cshperspect.a023671.
Prions are proteins that can adopt self-perpetuating conformations and are traditionally regarded as etiological agents of infectious neurodegenerative diseases in humans, such as Creutzfeldt-Jakob disease, kuru, and transmissible encephalopathies. More recently, a growing consensus has emerged that prion-like, self-templating mechanisms also underlie a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease, and Huntington's disease. Perhaps most surprising, not all prion-like aggregates are associated with pathological changes. There are now several examples of prion-like proteins in mammals that serve positive biological functions in their aggregated state. In this review, we discuss functional prions in the nervous system, with particular emphasis on the cytoplasmic polyadenylation element-binding protein (CPEB) and the role of its prion-like aggregates in synaptic plasticity and memory. We also mention a more recent example of a functional prion-like protein in the brain, TIA-1, and its role during stress. These studies of functional prion-like proteins have provided a number of generalizable insights on how prion-based protein switches may operate to serve physiological functions in higher eukaryotes.
朊病毒是一种能够呈现自我延续构象的蛋白质，传统上被视为人类传染性神经退行性疾病的病原体，如克雅氏病、库鲁病和传染性脑病。最近，越来越多的人达成共识，即朊病毒样的自我模板机制也是多种神经退行性疾病的基础，包括肌萎缩侧索硬化症、阿尔茨海默病和亨廷顿舞蹈症。也许最令人惊讶的是，并非所有朊病毒样聚集体都与病理变化相关。现在有几个哺乳动物中朊病毒样蛋白质的例子，它们在聚集状态下起积极的生物学功能。在这篇综述中，我们讨论神经系统中的功能性朊病毒，特别强调细胞质聚腺苷酸化元件结合蛋白（CPEB）及其朊病毒样聚集体在突触可塑性和记忆中的作用。我们还提到了大脑中一种功能性朊病毒样蛋白质TIA-1的最新例子及其在应激过程中的作用。这些对功能性朊病毒样蛋白质的研究为基于朊病毒的蛋白质开关如何在高等真核生物中发挥生理功能提供了许多可推广的见解。
